395 research outputs found
What advice are oncologists and surgeons in the United Kingdom giving to breast cancer patients about physical activity?
Evidence has shown that physical activity may attenuate the negative physical, psychological and functional effects of treatment in women diagnosed with breast cancer. Physical activity levels also decline substantially during and after completion of treatment for cancer, highlighting the importance of strategies to promote participation in regular physical activity in this population. Oncologists and surgeons may serve as an influential source of motivation to be physically activity in cancer patients, by conveying the importance of a healthy lifestyle. The primary purpose of the present study was to investigate whether oncologists and surgeons routinely discuss physical activity with their breast cancer patients and to investigate the nature of any information/advice provided during consultations. A secondary aim was to examine whether physically active oncologists and surgeons were more likely to provide advice about physical activity to patients, than inactive oncologists and surgeons. A brief postal questionnaire was sent to 710 consultant breast cancer oncologists and surgeons throughout the UK and 102 responded (response rate = 14.4%). Of responders, most (55.9%) did not routinely discuss physical activity with their patients. Amongst oncologists/surgeons (clinicians) who did offer advice, most focussed on discussing the benefits of physical activity for physical and functional health gains and for facilitating weight control and maintenance. A number of clinicians indicated they advised patients that physical activity may decrease risk of recurrence and improve survival, despite the lack of evidence from RCTs to support this suggestion. There was no significant association between the physical activity status of oncologists/surgeons and the likelihood that they discussed physical activity with patients. Educational strategies aimed at encouraging clinicians to promote physical activity in consultations need to be targeted widely amongst the cancer clinician community
All Six Planets Known to Orbit Kepler-11 Have Low Densities
The Kepler-11 planetary system contains six transiting planets ranging in
size from 1.8 to 4.2 times the radius of Earth. Five of these planets orbit in
a tightly-packed configuration with periods between 10 and 47 days. We perform
a dynamical analysis of the system based upon transit timing variations
observed in more than three years of \ik photometric data. Stellar parameters
are derived using a combination of spectral classification and constraints on
the star's density derived from transit profiles together with planetary
eccentricity vectors provided by our dynamical study. Combining masses of the
planets relative to the star from our dynamical study and radii of the planets
relative to the star from transit depths together with deduced stellar
properties yields measurements of the radii of all six planets, masses of the
five inner planets, and an upper bound to the mass of the outermost planet,
whose orbital period is 118 days. We find mass-radius combinations for all six
planets that imply that substantial fractions of their volumes are occupied by
constituents that are less dense than rock. The Kepler-11 system contains the
lowest mass exoplanets for which both mass and radius have been measured.Comment: 39 pages, 10 figure
<i>Plasmodium </i>Condensin Core Subunits SMC2/SMC4 Mediate Atypical Mitosis and Are Essential for Parasite Proliferation and Transmission
Condensin is a multi-subunit protein complex regulating chromosome condensation and segregation during cell division. In Plasmodium spp., the causative agent of malaria, cell division is atypical and the role of condensin is unclear. Here we examine the role of SMC2 and SMC4, the core subunits of condensin, during endomitosis in schizogony and endoreduplication in male gametogenesis. During early schizogony, SMC2/SMC4 localize to a distinct focus, identified as the centromeres by NDC80 fluorescence and chromatin immunoprecipitation sequencing (ChIP-seq) analyses, but do not form condensin I or II complexes. In mature schizonts and during male gametogenesis, there is a diffuse SMC2/SMC4 distribution on chromosomes and in the nucleus, and both condensin I and condensin II complexes form at these stages. Knockdown of smc2 and smc4 gene expression reveals essential roles in parasite proliferation and transmission. The condensin core subunits (SMC2/SMC4) form different complexes and may have distinct functions at various stages of the parasite life cycle
An Unusual Transmission Spectrum for the Sub-Saturn KELT-11b Suggestive of a Sub-Solar Water Abundance
We present an optical-to-infrared transmission spectrum of the inflated
sub-Saturn KELT-11b measured with the Transiting Exoplanet Survey Satellite
(TESS), the Hubble Space Telescope (HST) Wide Field Camera 3 G141 spectroscopic
grism, and the Spitzer Space Telescope (Spitzer) at 3.6 m, in addition to
a Spitzer 4.5 m secondary eclipse. The precise HST transmission spectrum
notably reveals a low-amplitude water feature with an unusual shape. Based on
free retrieval analyses with varying molecular abundances, we find strong
evidence for water absorption. Depending on model assumptions, we also find
tentative evidence for other absorbers (HCN, TiO, and AlO). The retrieved water
abundance is generally solar (0.001--0.7 solar
over a range of model assumptions), several orders of magnitude lower than
expected from planet formation models based on the solar system metallicity
trend. We also consider chemical equilibrium and self-consistent 1D
radiative-convective equilibrium model fits and find they too prefer low
metallicities (, consistent with the free retrieval
results). However, all the retrievals should be interpreted with some caution
since they either require additional absorbers that are far out of chemical
equilibrium to explain the shape of the spectrum or are simply poor fits to the
data. Finally, we find the Spitzer secondary eclipse is indicative of full heat
redistribution from KELT-11b's dayside to nightside, assuming a clear dayside.
These potentially unusual results for KELT-11b's composition are suggestive of
new challenges on the horizon for atmosphere and formation models in the face
of increasingly precise measurements of exoplanet spectra.Comment: Accepted to The Astronomical Journal. 31 pages, 20 figures, 7 table
Adjuvant tamoxifen and exemestane in postmenopausal early breast cancer:ten-year analysis of the randomised phase III TEAM trial
Surgical oncolog
Breast Cancer Index is a predictive biomarker of treatment benefit and outcome from extended tamoxifen therapy: final analysis of the Trans-aTTom study
PURPOSE: The Breast Cancer Index (BCI) HOXB13/IL17BR (H/I) ratio predicts benefit from extended endocrine therapy in hormone receptor–positive (HR(+)) early-stage breast cancer. Here, we report the final analysis of the Trans-aTTom study examining BCI (H/I)'s predictive performance. EXPERIMENTAL DESIGN: BCI results were available for 2,445 aTTom trial patients. The primary endpoint of recurrence-free interval (RFI) and secondary endpoints of disease-free interval (DFI) and disease-free survival (DFS) were examined using Cox proportional hazards regression and log-rank test. RESULTS: Final analysis of the overall study population (N = 2,445) did not show a significant improvement in RFI with extended tamoxifen [HR, 0.90; 95% confidence interval (CI), 0.69–1.16; P = 0.401]. Both the overall study population and N0 group were underpowered due to the low event rate in the N0 group. In a pre-planned analysis of the N(+) subset (N = 789), BCI (H/I)-High patients derived significant benefit from extended tamoxifen (9.7% absolute benefit: HR, 0.33; 95% CI, 0.14–0.75; P = 0.016), whereas BCI (H/I)-Low patients did not (−1.2% absolute benefit; HR, 1.11; 95% CI, 0.76–1.64; P = 0.581). A significant treatment-to-biomarker interaction was demonstrated on the basis of RFI, DFI, and DFS (P = 0.037, 0.040, and 0.025, respectively). BCI (H/I)-High patients remained predictive of benefit from extended tamoxifen in the N(+)/HER2(−) subgroup (9.4% absolute benefit: HR, 0.35; 95% CI, 0.15–0.81; P = 0.047). A three-way interaction evaluating BCI (H/I), treatment, and HER2 status was not statistically significant (P = 0.849). CONCLUSIONS: Novel findings demonstrate that BCI (H/I) significantly predicts benefit from extended tamoxifen in HR(+) N(+) patients with HER2(−) disease. Moreover, BCI (H/I) demonstrates significant treatment to biomarker interaction across survival outcomes
Soluble inflammatory mediators of synoviocytes stimulated by monosodium urate crystals induce the production of oxidative stress, pain, and inflammation mediators in chondrocytes
Brief report[Abstract] We hypothesized that the secretion of inflammatory mediators from synoviocytes affects the chondrocyte homeostasis of articular cartilage. This study was a preliminary attempt to elucidate the molecular mechanisms by which soluble mediators obtained from activated synoviocytes induce oxidative stress and inflammation in chondrocytes. We measured the concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), nerve growth factor (NGF), superoxide anion (O2•-), hydrogen peroxide (H2O2), and nitric oxide (NO•) from articular human cells. First, we created a conditional basal medium by exposing synoviocytes (HS) to monosodium urate crystals (CBM). The chondrocytes were exposed to either CBM (CCM), urate crystals directly (CMSU), or remained untreated (CC) as a negative control. Data were analyzed by ANOVA tests; Bonferroni test was performed for multiple comparisons between groups. Interestingly, we observed that mediators of inflammation and oxidative stress were significantly higher in CCM than CMSU and CC groups (P<0.01). The specific concentrations were as follows: 19.85 ng/mL of IL-6, 9.79 ng/mL of IL-8, 5.17 ng/mL of NGF, and 11.91 ng/mL of MCP-1. Of note, we observed the same trend for reactive oxygen and nitrogen species (P<0.001). Soluble mediators secreted by synoviocytes after being activated with MSU crystals (as observed in individuals who present gout attacks) trigger chondrocyte activation intensifying the articular inflammatory, oxidative, and pain states that damage cartilage in OA; this damage is more severe even when compared to HC directly exposed to monosodium urate crystals. Key Points • The molecular relation between MSU depositions and cartilage damage could be mediated by pro-inflammatory soluble mediators and oxidative molecules. • The secretion of pro-inflammatory mediators by activated synoviocytes is more harmful to chondrocytes than a direct activation in the chondrocyte culture. • Under this model, there is an important imbalance in the matrix homeostasis due to changes in several chemokines, cytokines, and other factors such as NGF, as well as oxidative mediators
Impact of age on efficacy and toxicity of nilotinib in patients with chronic myeloid leukemia in chronic phase : ENEST1st subanalysis
Purpose Achievement of deep molecular response with a tyrosine kinase inhibitor in patients with chronic myeloid leukemia (CML) is required to attempt discontinuation of therapy in these patients. The current subanalysis from the Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) study evaluated whether age has an impact on the achievement of deeper molecular responses or safety with frontline nilotinib in patients with CML. Methods ENEST1st is an open-label, multicenter, single-arm, prospective study of nilotinib 300 mg twice daily in patients with newly diagnosed CML in chronic phase. The patients were stratified into the following 4 groups based on age: young (18-39 years), middle age (40-59 years), elderly (60-74 years), and old (>= 75 years). The primary end point was the rate of molecular response 4 ([MR4] BCR-ABL1 Results Of the 1091 patients enrolled, 1089 were considered in the analysis, of whom, 23% (n = 243), 45% (n = 494), 27% (n = 300), and 5% (n = 52) were categorized as young, middle age, elderly, and old, respectively. At 18 months, the rates of MR4 were 33.9% (95% confidence interval [CI], 27.8-40.0%) in the young, 39.6% (95% CI, 35.3-44.0%) in the middle-aged, 40.5% (95% CI, 34.8-46.1%) in the elderly, and 35.4% (95% CI, 21.9-48.9%) in the old patients. Although the incidence of adverse events was slightly different, no new specific safety signals were observed across the 4 age groups. Conclusions This subanalysis of the ENEST1st study showed that age did not have a relevant impact on the deep molecular response rates associated with nilotinib therapy in newly diagnosed patients with CML and eventually on the eligibility of the patients to attempt treatment discontinuation.Peer reviewe
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